Navarese EP, et al. - Researchers performed meta-analyses and meta-regressions to assess if baseline low-density lipoprotein cholesterol (LDL-C) level linked to total and cardiovascular mortality risk reductions. They noted that, in trials of patients with higher baseline LDL-C levels, a greater reduction in risk of total and cardiovascular mortality was seen with more intensive compared with less intensive LDL-C lowering. This association disappeared when baseline LDL-C level was less than 100 mg/dL, indicating that patients with higher baseline LDL-C levels might see the most benefit from LDL-C–lowering therapy.

Methods

• A search of electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) was conducted through February 2, 2018 to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies.
• Data was abstracted and risks of bias was appraised by two investigators.
• Researchers categorized intervention groups as “more intensive” (more potent pharmacologic intervention) or “less intensive” (less potent, placebo, or control group).
• Total mortality and cardiovascular mortality were the coprimary end points.
• They undertook random-effects meta-regression and meta-analyses to evaluate connections between baseline LDL-C level and reductions in mortality end points and secondary end points, including major adverse cardiac events (MACE).

Results

• Researchers recognized 34 trials, with 136,299 patients receiving more intensive and 133,989 receiving less intensive LDL-C lowering.
• For more vs less intensive therapy, all-cause mortality was lower (7.08% vs 7.70%; rate ratio [RR], 0.92 [95% CI, 0.88 to 0.96]); however, there were variations by baseline LDL-C level.
• Meta-regression showed more intensive LDL-C lowering was correlated with higher decline in all-cause mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.91 [95% CI, 0.86 to 0.96]; P=.001; absolute risk difference [ARD], -1.05 incident cases per 1000 person-years [95% CI, -1.59 to -0.51]); however, in meta-analysis, this was observed only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction).
• With more intensive therapy, cardiovascular mortality was lower compared to less intensive therapy (3.48% vs 4.07%; RR, 0.84 [95% CI, 0.79 to 0.89]); however, this varied by baseline LDL-C level.
• In a meta-analysis, trials with baseline LDL-C levels of 160 mg/dL or greater showed the greatest reduction in all-cause mortality (RR, 0.72 [95% CI, 0.62 to 0.84]; P < .001; 4.3 fewer deaths per 1000 person-years).
• Progressively greater risk reductions with higher baseline LDL-C level for myocardial infarction, revascularization, and MACE was correlated with more intensive LDL-C lowering.